A chemical screen identifies trifluoperazine as an inhibitor of glioblastoma growth

• Published in: Biochemical and biophysical research communications 2017-12, Vol.494 (3-4), p.477-483
• Main Authors: Pinheiro, Tiago, Otrocka, Magdalena, Seashore-Ludlow, Brinton, Rraklli, Vilma, Holmberg, Johan, Forsberg-Nilsson, Karin, Simon, András, Kirkham, Matthew
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Cancer; Cell Line, Tumor; Cell lines; Cell Proliferation - drug effects; Cell Survival - drug effects; Dopamine; Dopamine Antagonists - administration & dosage; Dose-Response Relationship, Drug; Drug Discovery - methods; Drug Screening Assays, Antitumor - methods; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; Medicin och hälsovetenskap; Receptors, Dopamine - metabolism; Screening; Trifluoperazine; Trifluoperazine - administration & dosage
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2017.10.106

Glioblastoma (GBM) is regarded as the most common malignant brain tumor but treatment options are limited. Thus, there is an unmet clinical need for compounds and corresponding targets that could inhibit GBM growth. We screened a library of 80 dopaminergic ligands with the aim of identifying compounds capable of inhibiting GBM cell line proliferation and survival. Out of 45 active compounds, 8 were further validated. We found that the dopamine receptor D2 antagonist trifluoperazine 2HCl inhibits growth and proliferation of GBM cells in a dose dependent manner. Trifluoperazine's inhibition of GBM cells is cell line dependent and correlates with variations in dopamine receptor expression profile. We conclude that components of the dopamine receptor signaling pathways are potential targets for pharmacological interventions of GBM growth. •Screening of GBM cells uncovers 45 active dopaminergic ligands and 8 were validated.•Ligand selectivity suggests dopamine-mediated cell viability regulation in GBM.•The DRD2 antagonist trifluoperazine inhibits cell viability and growth of GBM cells.•DR expression profile of GBM cells alter the susceptibility to trifluoperazine.